Condensin I and condensin II proteins form a LINE-1 dependent super condensin complex and cooperate to repress LINE-1

Abstract

Condensin I and condensin II are multi-subunit complexes that are known for their individual roles in genome organization and preventing genomic instability. However, interactions between condensin I and condensin II subunits and cooperative roles for condensin I and condensin II, outside of their genome organizing functions, have not been reported. We previously discovered that condensin II cooperates with Gamma Interferon Activated Inhibitor of Translation (GAIT) proteins to associate with Long INterspersed Element-1 (LINE-1 or L1) RNA and repress L1 protein expression and the retrotransposition of engineered L1 retrotransposition in cultured human cells. Here, we report that the L1 3′UTR is required for condensin II and GAIT association with L1 RNA, and deletion of the L1 RNA 3′UTR results in increased L1 protein expression and retrotransposition. Interestingly, like condensin II, we report that condensin I also binds GAIT proteins, associates with the L1 RNA 3′UTR, and represses L1 retrotransposition. We provide evidence that the condensin I protein, NCAPD2, is required for condensin II and GAIT protein association with L1 RNA. Furthermore, condensin I and condensin II subunits interact to form a L1-dependent super condensin complex (SCC) which is located primarily within the cytoplasm of both transformed and primary epithelial cells. These data suggest that increases in L1 expression in epithelial cells promote cytoplasmic condensin protein associations that facilitate a feedback loop in which condensins may cooperate to mediate L1 repression.

Expression of retrotransposons contributes to aging inDrosophila

“…NRTIs are well-established to block retrotransposon replication thereby preventing RT reinsertion (14). However, RT inhibitor treatment can additionally decrease RNA levels of the L1 element in human cells, thus the effect of these drugs may not be limited to restricting mobilization (49). If NTRIs exert similar effects in flies, the extended lifespan seen using these drugs could be due to reduced expression of some or all TEs, rather than changes to replicative capacity.…”

“…By combining a single nucleus whole genome sequencing approach with analyses using two pipelines, we are confident that new insertions would have been detected if present. Prior to our study, the most compelling data indicating increased TE insertions with age in wild-type animals came from use of a TE reporter transgene and sequencing of bulk DNA samples (24, 27, 49). Use of a fluorescent reporter for the RT mdg4 revealed age-associated de novo insertions in cells of the adult brain and fat body, although the frequency was low (23, 26).…”

Condensin-mediated restriction of retrotransposable elements facilitates brain development inDrosophila melanogaster

“…Condensins interact with DNA to promote efficient chromatin condensation and ensure that equal division of genetic material occurs during mitosis [18][19][20][21][22][23] . Our lab previously identified new roles for condensin I and condensin II in the repression of retrotransposable elements (RTEs) in both human cells 24,25 and Drosophila cells and tissues 26 . RTEs are DNA elements that can copy and 4 paste themselves into other areas of the genome through the process of retrotransposition which involves the generation of cDNA by an RTE-encoded reverse transcriptase 27 .…”

NCAPD2 serves as a potential prognostic biomarker for lung adenocarcinoma and promotes cell proliferation, migration, invasion and cell cycle <i>in vitro</i>

“…Condensin I and condensin II are distinct forms of condensin protein complexes found in various eukaryotic cells [13], assembling and segregating chromosomes during both mitosis and meiosis [14]. Furthermore, they may assume specific functions in the context of innate immune responses [15][16][17]. The regulatory influence of condensin I on gene expression has been demonstrated, and evidence suggests a potential correlation between the dysregulation of condensin I and the development of cancer [17][18][19].…”

“…Furthermore, they may assume specific functions in the context of innate immune responses [15][16][17]. The regulatory influence of condensin I on gene expression has been demonstrated, and evidence suggests a potential correlation between the dysregulation of condensin I and the development of cancer [17][18][19]. As a component of condensin I, NCAPD2 is implicated in a range of diseases, including Alzheimer's disease, microcephaly, Parkinson's disease, and various neurodevelopmental disorders [20][21][22].…”